NY-ESO-1 expression is tightly linked to TMPRSS2-ERG fusion in prostate cancer

Grupp, Katharina; Ospina-Klinck, Daniel; Koop, Christina; Wilczak, Waldemar; Adam, Meike; Simon, Ronald; Sauter, Guido; Izbicki, Jakob R.; Graefen, Markus; Huland, Hartwig; Steurer, Stefan; Schlomm, Thorsten; Minner, Sarah; Quaas, Alexander

doi:10.1002/pros.22816

Cited by 10 publications

(3 citation statements)

References 45 publications

(83 reference statements)

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“…Accordingly, independent prognostic relevance was seen for SENP1 expression in this particular subgroup. In earlier studies, we have identified other molecular markers that seemed to exert their prognostic impact only in specific molecularly defined subgroups such as in ERG positive and PTEN deleted cancers [ 49 , 50 ], ERG negative cancers lacking PTEN deletion [ 51 ], ERG positive cancers [ 25 ], ERG negative cancers [ 52 ], cancers lacking PTEN deletion [ 53 , 54 ], or in all cancers irrespective of ERG and PTEN status [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of SUMO1/Sentrin specific peptidase 1 (SENP1) in prostate cancer is limited to ERG-fusion positive tumors lacking PTEN deletion

et al. 2015

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BackgroundPosttranscriptional protein modification by SUMOylation plays an important role in tumor development and progression. In the current study we analyzed prevalence and prognostic impact of the de-SUMOylation enzyme SENP1 in prostate cancer.MethodsSENP1 expression was analyzed by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancer specimens. Results were compared to tumor phenotype, ERG status, genomic deletions of 3p, 5q, 6q and PTEN, and biochemical recurrence.ResultsSENP1 immunostaining was detectable in 34.5 % of 9,516 interpretable cancers and considered strong in 7.3 %, moderate in 14.9 % and weak in 12.3 % of cases. Strong SENP1 expression was linked to advanced pT stage (p < 0.0001), high Gleason grade (p < 0.0001), positive lymph node status (p = 0.0019), high pre-operative PSA levels (p = 0.0037), and PSA recurrence (p < 0.0001). SENP1 expression was strongly associated with positive ERG fusion status as determined by both in situ hybridization (FISH) and immunohistochemistry as well as with PTEN deletions. Detectable SENP1 immunostaining was found in 41 % of ERG positive and in 47 % of PTEN deleted cancers but in only 30 % of ERG negative and 30 % of PTEN non-deleted cancers (p < 0.0001 each). Deletions of 3p, 5q, and 6q were unrelated to SENP1 expression. Subset analyses revealed that the prognostic impact of SENP1 expression was solely driven by the subgroup of ERG positive, PTEN undeleted cancers. In this subgroup, the prognostic role of SENP1 expression was independent of the preoperative PSA level, tumor stage, Gleason grade, and the status of the resection margin.ConclusionsSENP1 expression has strong prognostic impact in a molecularly defined subset of cancers. This is per se not surprising as the biologic impact of each individual molecular event is likely to be dependent on its cellular environment. However, such findings challenge the concept of finding clinically relevant molecular signatures that are equally applicable to all prostate cancers.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1555-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The prognostic value of SUMO1/Sentrin specific peptidase 1 (SENP1) in prostate cancer is limited to ERG-fusion positive tumors lacking PTEN deletion

et al. 2015

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“…In several of these, a prognostic impact was only seen for ERG-negative, but not for ERG-positive cancers [38,39,40]. The present study demonstrates that GGH belongs to this type of proteins.…”

Section: Discussionmentioning

confidence: 52%

High-Level γ-Glutamyl-Hydrolase (GGH) Expression is Linked to Poor Prognosis in ERG Negative Prostate Cancer

Melling

Rashed

Schroeder

et al. 2017

IJMS

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γ-glutamyl-hydrolase (GGH) is a ubiquitously-expressed enzyme that regulates intracellular folate metabolism for cell proliferation, DNA synthesis, and repair. Employing GGH immunohistochemistry on a tissue microarray with 12,427 prostate cancers, we found that GGH expression was negative to low in normal prostate epithelium, whereas 88.3% of our 10,562 interpretable cancers showed GGH expression. GGH staining was considered as low intensity in 49.6% and as high intensity in 38.6% of cancers. High GGH expression was linked to the TMPRSS2:ERG-fusion positive subset of cancers (p < 0.0001), advanced pathological tumor stage, and high Gleason grade (p < 0.0001 each). Further analysis revealed that these associations were merely driven by the subset of ERG-negative cancers, High GGH expression was weakly linked to early biochemical recurrence in ERG negative cancers (p < 0.0001) and independent from established histo-pathological parameters. Moreover, GGH expression was linked to features of genetic instability, including presence of recurrent deletions at 3p, 5q, 6q, and 10q (PTEN, p ≤ 0.01 each), as well as to accelerated cell proliferation as measured by Ki67 immunohistochemistry (p < 0.0001). In conclusion, the results of our study identify GGH as an ERG subtype specific molecular marker with modest prognostic relevance, which may have clinical relevance if analyzed in combination with other molecular markers.

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“…On the other hand, in non-Hodgkin's lymphoma the higher positivity for NY-ESO-1 has been observed in early stage compared with advanced stage disease [58]. In prostate cancer, a tight link has been observed between NY-ESO-1 expression and ERG activation and (to a lesser extent) PTEN-and 6q15-deletions [59]. In a subset of tumors, NY-ESO-1 expression has been shown to be lost during remission which is thought to be either a means to evade T-cell-based immunosurveillance or the result of reduced cell proliferation.…”

Section: Ny-eso-1 Expression Pattern In Tumorsmentioning

confidence: 95%

New York Esophageal Squamous Cell Carcinoma-1 and Cancer Immunotherapy

Esfandiary

Ghafouri‐Fard

2015

Immunotherapy

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New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a known cancer testis gene with exceptional immunogenicity and prevalent expression in many cancer types. These characteristics have made it an appropriate vaccine candidate with the potential application against various malignancies. This article reviews recent knowledge about the NY-ESO-1 biology, function, immunogenicity and expression in cancers as well as and the results of clinical trials with this antigen.

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NY-ESO-1 expression is tightly linked to TMPRSS2-ERG fusion in prostate cancer

Cited by 10 publications

References 45 publications

The prognostic value of SUMO1/Sentrin specific peptidase 1 (SENP1) in prostate cancer is limited to ERG-fusion positive tumors lacking PTEN deletion

The prognostic value of SUMO1/Sentrin specific peptidase 1 (SENP1) in prostate cancer is limited to ERG-fusion positive tumors lacking PTEN deletion

High-Level γ-Glutamyl-Hydrolase (GGH) Expression is Linked to Poor Prognosis in ERG Negative Prostate Cancer

New York Esophageal Squamous Cell Carcinoma-1 and Cancer Immunotherapy

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